Testing Miglustat Administration in Subjects With Spastic Paraplegia 11

Phase 2

Completed

• Conditions: Hereditary Spastic Paraparesis
• Interventions: Drug: Miglustat 100 MG

• Registration Number: NCT04768166
• Lead Sponsor: IRCCS Fondazione Stella Maris

Brief Summary

Hereditary spastic paraparesis type 11 (SPG11) is caused by mutations in the SPG11 gene that produces spatacsin, a protein involved in lysosomal function. Studies performed in skin cells (fibroblasts) from SPG11 patients, mice and zebrafish models of the disease showed that the material accumulated in the lysosomes is made of glycosphingolipids (GSL).

Miglustat is a drug that inhibits an enzyme called glucosylceramide synthetase (GCS) which is used for the production of GSL. Miglustat, therefore, helps to delay the production of GSL. This study aims to collect preliminary data on the safety of miglustat on the SPG11 disease and to assess biomarkers.

Detailed Description

We will analyze the safety of Miglustat

Study Timeline

• Study First Submitted: 2021-02-12
• Study First Submitted QC: 2021-02-22
• Study First Posted: 2021-02-24
• Study Start: 2021-06-15
• Primary Completion: 2021-08-30
• Study Completion: 2021-09-15
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-01
• Last Update Posted: 2022-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

• Written signed informed consent;
• Confirmed diagnosis of SPG11;
• Age > 13 years;
• SPRS score ≥ 10 or ≤35;
• Use of effective contraceptive methods and the performance of pregnancy tests (only fertile subjects).

Exclusion Criteria

• Diagnosis of other concomitant neurodegenerative diseases;
• Outcomes of severe pre- or peri-natal suffering;
• Age ≤ 13 years;
• SPRS score ≥ 35 or ≤10;
• Hypersensitivity or intolerance to miglustat;
• Participation in other pharmacological studies within 30 days of the first Study visit (T0);
• The inability to take the drug;
• Any additional medical conditions;
• Subjects with severe renal impairment;
• Refusal to use effective contraceptive methods and the performance of pregnancy tests (only fertile subjects).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Evaluate the safety of Miglustat administration in subjects with Spastic Paraplegia 11	Miglustat 100 MG	100 mg of Miglustat, 3 caps per day for first 4 weeks; 100 mg of Miglustat, 6 caps per day for 8 weeks

Primary Outcome Measures

Name	Time	Method
1-Changes from baseline blood tests at 24 weeks 2-Changes from baseline neurophysiological tests at 24 weeks 3-Report of severe adverse events	At baseline, 24 weeks	routine blood test

Secondary Outcome Measures

Name	Time	Method
Changes from baseline GM2/GM3 levels at 24 weeks	At baseline, 24 weeks	lipid assessments
Assess changes in the scores of the Spastic Paraplegia Rating Scale (SPRS) at 24 weeks	At baseline, 24 weeks	SPRS rates disease severity (0-52) with lower numbers indicating less impairement

Trial Locations

Locations (1)

IRCCS Fondazione Stella Maris; 🇮🇹 Pisa, PI, Italy